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Aloe Vera

(Source: SaluGenecists, Inc.)

Summary

Aloe vera is a perennial plant with yellow flowers and tough fleshy triangular or spear-like leaves that grow in a rosette configuration. Although historical records indicate that aloe may have originated in Egypt or the Middle East, it has been introduced and is naturalized in most of the tropics and warmer regions of the world including the Caribbean, the southern U.S., Mexico, Latin America, the Middle East, India and other parts of Asia.

Aloe vera's medicinal use can be traced to antiquity with Mesopotamian clay tablets dated as early as 1750 BC indicating that aloe vera was used for medicinal purposes. Aloe vera is still widely used in many traditional systems of medicine and has been adopted into the materia medicas of many cultures of the world.

Both the leaves inner layer and the corrugated lining just below the outer layer are the sources of the constituents used medicinally. The key constituents of aloe include anthraquinones, saccharides, prostanoids, and superoxide dismutases. The typical forms of aloe vera used include gel, gel concentrate and juice. It is used both orally and topically.

Aloe vera's diverse pharmacological actions as a laxative, cathartic, immune potentiatior, antimicrobial and wound-healing agent provide a scientific basis for its wide ranging folk use and clinical applications. In small doses, its anthroquinone aloin acts as a digestive system tonic, improving intestinal muscle tone while at higher dosages, it is a strong purgative, acting primarily on the large intestine where it increases colonic secretions and peristaltic contractions. Aloe vera gel has also been shown to inhibit excessive secretion of hydrochloric acid, promote improved protein digestion and reduce bacterial putrefaction.

Its immune-enhancing and antimicrobial activities include its antibacterial, antifungal, antiviral and anti-inflammatory properties. These qualities in addition to its emollient characteristics support the beneficial topical effects that aloe vera has on wound healing.

Owing to its varied pharmacological actions, aloe vera is used for a variety of conditions including burns, frost bite, and other tissue damage; psoriasis; gastric ulcers; AIDS; asthma; diabetes; contraception; and cancer prevention.

Side effects from orally ingested aloe vera may include abdominal pain and cramping, diarrhea, muscle weakness and potassium depletion. Owing to the irritating effects of its purgative components as well as its suggested potential to cause potassium depletion, aloe vera is contraindicated for those with various gastrointestinal conditions, hemorrhoids, heart disease and kidney disease. Aloe-containing drug preparations (i.e., herbal stimulant laxative drugs) have a higher potential for toxicity than pure aloe vera.

Aloe vera may increase the risk of toxicity of a variety of drugs and botanicals used for diabetes and heart conditions while also potentially reducing the absorption of some drugs owing to its effect on gastrointestinal transit time. Additionally, it may exacerbate potassium loss caused by other drugs and botanicals.

Typical dosage varies depending upon the form being used and the health care application for which it is being used.

Key Constituents

Aloe vera contains numerous biologically active compounds, and unlike many botanical medicines, whose concentration of active principles can vary substantially depending upon where the plant is grown, commercial aloe's concentration of its major compounds, aloeresin-A, aloesin, and aloin is quite consistent. One study found that aloeresin A, aloesin, and aloin (both epimers A and B) invariably contributed between 70 and 97% of total dry weight, in a ratio of approximately 4:3:2, respectively.

Minor compounds, howver, were less evenly distributed. Aloe from Western countries was found to contain higher concentrations of aloinoside A and aloinoside B. The aloin content of the exudate also varied, but no distinct geographical discontinuities were noted.

In 1851, the cathartic action of aloe was revealed to be due to aloin, a lemon yellow powder formed from drying the bitter latex of the corrugated layer. Several anthracenes have been isolated from this powder, the major anthraquinone being barbaloin. Barbaloin and aloin are often referred to synonymously. Aloe also contains other anthraquinone derivatives, including the anthracene known as aloe-emodin, but barbaloin is the most potent cathartic. As a whole, the anthraquinone compounds are water-soluble glycosides easily separated from the water-insoluble resinous material.

Saccharides

Recent research on aloe vera has targeted its glycoprotein, mucopolysaccharide, and polysaccharide constituents. Aloe contains the polysaccharides galactose, xylose, arabinose, and acetylated mannose (acemannan). Mannose is a polysaccharide similar to guar and locust bean. Acemannan, a water-soluble, long-chain polydispersed beta-linked mannan polymer interspersed with O-acetyl groups, has been the object of much clinical research for its potential uses as an antiviral and immunopotentiating agent, especially in the treatment of AIDS.

Prostanoids

Several prostanoids have been discovered in aloe vera extracts, perhaps the most important of which is gamma-linolenic acid (C18:3). The conversion of essential fatty acids to prostanoids by the enzyme cyclooxygenase in a plant such as aloe vera is quite rare. The major unsaturated fatty acid in the plant is gamma-linolenic acid (C18:3), which can be converted to eicosatrienoic acid, the precursor to 1 series prostaglandins, which are known to exert beneficial effects on inflammation, allergy, platelet aggregation, and wound healing. Aloe's combination of gamma linolenic acid (GLA) and/or series 1 prostaglandins in a stable medium, along with inhibitors of thromboxane synthesis, provides a unique mix of chemical characteristics and may be a primary factor in aloe's wound healing effects.

Superoxide dismutase

Extracts from the inner parenchymatous leaf gel as well as the rind of Aloe barbadensis Miller have been shown to contain seven electrophoretically identifiable superoxide dismutases (SODs). Two are mangano-SODs, while the other five are cupro-zinc SODs.

Aloe vera is still widely used in many traditional systems of medicine and has been adopted into the materia medicas of many cultures of the world. In India, for example, in addition to its topical applications, aloe (whole leaves, the exudate, and the fresh gel) is used as a cathartic, stomachic, and anthelmintic. Aloe vera's use in the United States can be traced as far back as the United States Pharmacopoeia of 1820, in which a number of aloe preparations are described, most of which take advantage of aloe's laxative effects. By the early 1900s, more than 27 different aloe preparations were in popular use in the US, and by 1920, aloe was being cultivated for pharmaceutical use.

In 1935, a group of physicians successfully used the fresh juice to treat a patient suffering from facial burns due to X-rays, initiating an important modern usage of aloe vera. Aloe's effectiveness in providing relief as a topical treatment of burns, minor irritations, skin ulcers, and other skin disorders has resulted in its inclusion in a wide variety of dermatologic and cosmetic formulations.

Today, aloe is still predominantly used without direct medical supervision, but research is confirming more of aloe's age-old medicinal applications and revealing new potentially beneficial effects of this bioactively diverse botanical.

Physiological Effects

Research on aloe vera's diverse pharmacological activities provides a scientific basis for its clinical application as a cathartic, immune potentiatior, antimicrobial and wound-healing agent.

Gastrointestinal Effects

Laxative actions

Physicians have prescribed whole aloe leaf as a purgative for more than 2,000 years; its active cathartic principle, aloin, was discovered in 1851. In small doses, aloin acts as a digestive system tonic, improving intestinal muscle tone. At higher dosages, however, it is a strong purgative, acting primarily on the large intestine where it increases colonic secretions and peristaltic contractions. For many years, aloin, in combination with strychnine and belladonna, was one of the most popular laxatives for chronic constipation. Today, other anthraquinone laxatives, e.g., cascara and senna, which are much less liikely than aloin to cause painful contraction, are much more popular.

Aloe's laxative effects continue to be analyzed by a substantial amount of research. Research using rat large intestine shows that barbaloin induces an increase in water content of the large intestine, which is then followed by the stimulation of peristalsis, resulting in diarrhea. Since the increase in water content is the initiating event, it is thought to be the more important factor in the barbaloin-induced diarrhea. Additional studies suggest that aloe-emodin-9-anthrone (AE-anthrone), which is produced from barbaloin in the rat large intestine, is the actual chemical mediator of this effect. AE-anthrone was found to not only cause an increase in the intestinal water content, but also to stimulate mucus secretion.

Bowel detoxification

In 1985, Bland reported the effect of orally consumed aloe vera juice on urinary indican, gastrointestinal pH, stool culture, and stool specific gravity in a semi-controlled study of 10 (five men and five women) healthy human subjects. After one full week of drinking 6 ounces of aloe vera juice three times daily, subjects' urinary indican levels decreased one full unit. Urinary indican is used as an indicator of the degree to which dietary protein is malabsorbed and/or intestinal bacteria are engaged in putrefactive processes. This significant drop in urinary indican levels suggests that regular aloe vera juice consumption may promote improved protein digestion and absorption and/or reduced bacterial putrefaction.

Inhibition of gastric acid secretion

In the same study, Heidelberg gastric analysis showed that aloe vera juice increased gastric pH by an average of 1.88 units, which supported the findings of other researchers that aloe vera gel can inhibit the secretion of hydrochloric acid. The Heidelberg test also demonstrated that aloe vera juice can slow down gastric emptying, another factor that may promote improved digestion.

Significant alterations in stool cultures were also noted in 6 of the 10 subjects after the week long study, implying that aloe vera juice may also exert bacteriostatic or fungistatic activity. In the four subjects whose baseline cultures were positive cultures for yeast, the number of yeast colonies was reduced.

In addition, although none of the subjects complained of diarrhea or loose stools while taking the aloe vera juice, their stool specific gravity was reduced after the week, suggesting improved water retention.

Immune-Enhancing and Antimicrobial Activity

Antibacterial and antifungal activity

Aloe has demonstrated activity against many common bacteria and fungi in several studies. In the most detailed of these studies, Robson et al. assayed the antimicrobial properties of an aloe vera extract and reviewed the work of others. Both mean inhibitory and mean lethal concentrations were determined and compared with silver sulfadiazine, a potent antiseptic used in the treatment of extensive burns. As the following table clearly shows, aloe vera was found to be a more effective antimicrobial agent compared to silver sulfadiazine against all organisms except for S. faecalis.

A 60% aloe vera extract was shown to be bactericidal against Pseudomonas aeruginosa, Klebsiella pneumoniae, Serratia marcescens, Citrobacter sp., Enterobacter cloacae, Streptococcus pyogenes, and Strep. agalacticae. Seventy per cent concentrations of aloe were bactericidal for Staphylococcus aureus, 80% for E. coli, and 90% for Streptococcus faecalis and Candida albicans. Organisms inhibited in other studies include Mycobacterium tuberculosis, Trichophyton sp., and Bacillus subtilis. The antimicrobial activity of aloe vera gel in a cream base against common skin pathogens was shown to be slightly better than silver sulfadiazine in agar well diffusion studies.

Acemannan in injectable form has been approved for veterinary use in fibrosarcomas and feline leukemia. Feline leukemia, like AIDS, is caused by a retrovirus (feline leukemia virus or FeLV) so lethal that once cats develop clinical symptoms, they are often euthanized. Typically, more than 70% of cats die within 8 weeks of onset of clinical signs. In a study of 44 cats with clinically confirmed feline leukemia, acemannan was injected (2mg/kg) weekly for 6 weeks, and the cats were re-examined 6 weeks after termination of treatment. At the end of the 12 week study, 71% of the cats were alive and in good health.

Immune enhancement

Acemannan is a potent immunostimulant. Studies have demonstrated acemannan's enhancement of macrophage release of interleukin-1-alpha, cytokines, tumor necrosis factor, and nitric oxide release, as well as phagocytosis and non-specific cytotoxicity. Acemannan has also been shown to enhance T-cell function and interferon production, possibly due to its enhancement of macrophage function. Macrophage production of cytokines IL-6 and TNF-alpha is dependent on the dose of acemannan provided and can be substantial. For example, in one study, acemannan enhanced the macrophage respiratory burst by atwofold increase above media controls, enhanced phagocytosis 45% compared to 25% in controls, and killed 38% of Candida albicans compared to 0-5% killing in controls.

Hematopoetic effects

Several complex carbohydrates have been found to significantly stimulate hematopoiesis including CARN 750, a polydispersed beta-(1,4)-linked acetylated mannan isolated from aloe vera. Subcutaneous injections of 1mg/ mouse of CARN 750 optimally increased hematopoietic progenitors, measured as interleukin-3-supported colony forming units-culture (CFU-C) and high proliferative potential colony-forming cells (HPP-CFC) assays in the spleen. Providing 2 mg/animal of CARN 750 optimally increased bone marrow cellularity, frequency and absolute number of HPP-CFCs and CFU-Cs. The hematopoietic activity of CARN 750 increased with the frequency of administration. The greatest increase in activity occurred in mice myelosuppressed with radiation.

Anti-inflammatory activity

Aloe vera's demonstrated anti-inflammatory actions include: blocking the generation of inflammatory mediators, i.e., thromboxanes and bradykinin; reducing neutrophil infiltration during inflammation; and reducing edema. Several compounds in aloe are responsible for these actions including its various anthraquinones, salicylates, and most important, its glycoproteins and a serine, carboxypeptidase, which have been shown to inhibit and actually break down bradykinin, a major mediator of pain and inflammation. These anti-inflammatory substances may be primary active agents in both topical and oral clinical applications.

One comprehensive study evaluated the effects of aqueous, chloroform, and ethanol extracts of aloe vera gel on carrageenan-induced edema in the rat paw, and neutrophil migration into the peritoneal cavity stimulated by carrageenan. The capacity of the aqueous extract to inhibit cyclooxygenase activity was also evaluated. The aqueous and chloroform extracts decreased the edema induced in the hind paw and the number of neutrophils migrating into the peritoneal cavity, while the ethanol extract only decreased the number of neutrophils. The aqueous extract was also found to inhibit prostaglandin E2 production from arachidonic acid, via inhibition of cyclooxygenase. The aqueous extract contained anthraglycosides, reductor sugars and cardiotonic glycosides; the ethanol extract contained saponins, carbohydrates, naftoquinones, sterols, triterpenoids and anthraquinones; and the chloroform extract contained sterols and anthraquinones.

Aloe also helps reduce inflammation through its free radical scavenging activiity and inhibition of lipid peroxidation. One study, using rat hepatocytes exposed to strong oxidizing agents, measured the activity of seven anthraquinones and four anthrones against non-enzymatic and enzymatic lipid peroxidation in vitro and their ability to scavenge free radicals. Dithranol and anthrone provided the strongest inhibition of non-enzymatic peroxidation. Rhein anthrone and aloe-emodin showed the highest inhibitory activity against peroxidation of linoleic acid catalyzed by lipoxygenase. Anthrone, dithranol and rhein anthrone were the most effective free radical scavengers.

Wound healing

Aloe vera's beneficial topical effects on wound healing are likely due to the combination of its anti-inflammatory, moisturizing, emollient, and antimicrobial actions. Aloe vera contains a number of compounds necessary for wound healing, including vitamin C, vitamin E and zinc. In addition, unlike many other anti-inflammatory substances, aloe vera has been shown to stimulate fibroblast and connective tissue formation, thereby promoting wound repair. Finally, aloe appears to stimulate the epidermal growth and repair process, presumably due to its polysaccharides. Mannose-6-phosphate, the major sugar in the aloe vera gel, may be its most active growth substance.

Aloe's effectiveness in wound healing has been further demonstrated by its ability to counteract cortisone's suppressive effects on wound healing. In one study, aloe vera at doses of 100 and 300mg/kg daily for 4 days blocked the wound healing suppression of hydrocortisone acetate up to 100% using the wound tensile strength assay. The authors suggested that the growth factors present in aloe vera masked the wound healing inhibitors.

Alcohol detoxification

Oral administration of aloin (300mg/kg) given 12 hours prior to the administration of alcohol (3.0g/kg) was shown to decrease the blood alcohol area under the curve by 40%, sugesting an increase in the rate of blood alcohol elimination from the body of 45-50%. Analysis of hepatic triglyceride (TG) levels revealed that both ethanol and the aloin, when given separately, significantly increased the TG levels in a comparable manner. However, the level obtained by the combined treatment of aloin and ethanol was not statistically different from that produced by either treatment alone. The levels of serum l-aspartate:2-oxoglutarate aminotransferase (AST) and l-alanine:2-oxoglutarate aminotransferase (ALT) activities were not increased by acute alcohol intoxication, aloin alone, or the combined treatment of alcohol and aloin.

Typical Use

Burns, frost bite, and other tissue damage

Although some human studies have been done, most of the research on aloe vera has utilized different animals in various models of inflammation and wound healing. Virtually all of the studies support the topical use of aloe vera gel, especially in minor burns or skin inflammation. Some recent research is now supporting its use even for more severe tissue damage.

The human research that has been done is promising. For example, in one study of three patients with chronic leg ulcers of 5, 7, and 15 years duration, aloe vera gel, applied to the ulcers on gauze bandages, rapidly reduced ulcer size in all three patients and completely resolved the ulcerations in two. Positive results using aloe vera gel for acne and seborrhea have also been reported.

In another human study of 27 patients with a partial-thickness burn wound, treatment with aloe vera gel was compared with vaseline gauze. Average healing time in the area treated with aloe gel was a statistically significant and dramatic 1 week shorter: 11.9 days compared with 18.2 days for the vaseline gauze treated wound. Histological evaluation showed early epithelialization in the aloe vera gel treated area.

An animal study compared the therapeutic effects of systemic pentoxifylline with topical aloe vera cream in the treatment of frostbite. Ten New Zealand white rabbits with frostbitten ears were assigned to one of four treatment groups: untreated controls, those treated with aloe vera cream, those treated with pentoxifylline, and those treated with both aloe vera cream and pentoxifylline. The control group had only a 6% tissue survival. In the rabbits given pentoxifyline, tissue survival increased to 20%, while in those treated with aloe vera cream, tissue survival increased to 24%. Rabbits receiving the combination therapy did the best with 30% tissue survival.

Aloe has been shown to effectively promote healing even in particularly severe tissue injuries, such as those seen in necrotizing fasciitis. Necrotizing fasciitis usually initially manifests as a low grade cellulitis, but quickly progresses to a limb and life-threatening soft tissue infection. Immediate surgical debridement is essential followed by aggressive wound management.

An interesting report describes excellent results using aloe vera in two cases. The first case was a 72-year-old female who, upon presenting to the ER with a "a sore bottom", was diagnosed with five problems: anal-rectal abscess, Fournier's gangrene, ulcerative enterocolitis, chronic blood loss/anemia, and protein caloric malnutrition. After debridement, her anal-rectal wound extended from the labia to the left buttock. Care was multidisciplinary and included applying a water-based aloe gel and saline-soaked gauze twice a day. After 45 days, the wound exhibited a pink base with granulation tissue and contraction of the wound edges.

The second case was a 48-year-old male with seroma of the left leg secondary to a crush injury. Within 3 days, he developed deep vein thrombosis in that leg as well as two large seroma cavities on either side of the thigh. Care included packing with aloe gel and saline soaked sponges. Two weeks after admission, the anterior wound was covered with a split thickness skin graft, although partial closure of the lateral cavity with retention sutures was attempted unsuccessfully. After 5 weeks treatment with aloe gel, healing was complete for the anterior wound and 95% complete for the posterior wound.

Radiation burns

During the 1930s, X-rays were used therapeutically for cancer, eczema and other skin complaints, and as a depilatory agent. In 1935, Collins & Collins reported the successful treatment of a woman with a patch of severe X-ray dermatitis on her forehead using aloe vera gel. The woman had tried various medical treatments for 8 months, but her condition continued to worsen. As a temporary measure before a skin graft, the Collins applied a preparation of fresh whole aloe vera leaves to reduce the itching. "Twenty-four hours later, she reported that the sensation of itching and burning had entirely subsided," and by 5 weeks, "there was complete regeneration of the skin of the forehead and scalp, new hair growth, complete restoration of sensation, and absence of scar." Complete healing occurred within five months. After this case report was published, other case reports followed, which, although not as dramatic as this case, clearly indicated that aloe vera could be effective in some cases.

Up until the 1940s, most of the studies on aloe were reported case histories. To evaluate these case reports, animal studies began to appear in the literature. Rowe and colleagues performed several studies in rats with radiation-induced ulcers and determined that fresh aloe pulp was effective, but dried aloe powder was not.

In 1953, Lushbaugh & Hale, working for the US Atomic Energy Commission, produced one of the most convincing studies of the efficacy of aloe vera gel. Twenty albino rats were exposed to beta-radiation and different treatments were used on quadrants of the affected area of each animal. The treatments used were fresh aloe vera leaf, a commercial aloe vera ointment, application of a dry gauze bandage, and an untreated control. Both fresh aloe vera and the aloe vera ointment produced clear improvements. At the end of 2 months, the aloe vera-treated areas were completely healed, while the other two areas had still not healed at the end of 4 months.

Doubt has been cast on aloe vera's efficacy for severe radiation burns by a recent, large, placebo-controlled, double-blind study that reported two Phase III randomized trials. The first double-blind study utilized a placebo gel, and involved 194 women receiving breast or chest wall irradiation. The second trial randomized 108 such patients to aloe vera gel vs. no treatment. Skin dermatitis was scored weekly during these trials both by patients and by health care providers. Skin dermatitis scores were virtually identical on both treatment arms during both of the trials.

This apparently contradictory result might be explained by a another recent study which compared the efficacy of commercially available gels with an acemannan-rich extract from aloe leaves in the treatment of irradiated mice. Male C3H mice received graded single doses of gamma radiation ranging from 30 to 47.5Gy to the right leg. In most experiments, the gel was applied daily, beginning immediately after irradiation. To determine the timing of application for best effect, gel was applied beginning on days -7, 0, or +7 relative to the day of irradiation (day 0) and continuing for 1, 2, 3, 4, or 5 weeks. The right inner thigh of each mouse was scored on a scale of 0 to 3.5 for severity of radiation reaction from the seventh to the 35th day after irradiation. Dose-response curves were obtained by plotting the percentage of mice that reached or exceeded a given peak skin reaction as a function of dose. While the acemannan-rich extract gel proved to be highly effective, the commercially available gel produced no improvement over the control. Additionally, the researchers found that the aloe gel had to applied immediately after irradiation and continued for at least 2 weeks. No effect occured if the aloe gel was applied only before irradiation or beginning 1 week after irradiation. This study clearly shows that the quality and concentration of aloe constituents are crucial if clinical results are to be obtained.

Psoriasis

A recent double-blind, placebo-controlled study evaluated the clinical efficacy and tolerability of topical aloe vera extract 0.5% in a hydrophilic cream on psoriasis. Sixty patients (36 male/24 female) aged 18-50 years (mean 25.6) with slight to moderate chronic plaque-type psoriasis and PASI (psoriasis area and severity index) scores between 4.8 and 16.7 (mean 9.3) were randomized to two groups. The mean duration of the disease prior to enrollment was 8.5 years (range 1-21). Patients self-administered trial medication topically at home three times daily for 5 consecutive days each week for a maximum 4 weeks of active treatment. Patients were examined on a weekly basis. Those showing a progressive reduction of lesions, desquamation followed by decreased erythema, infiltration and lowered PASI score were considered healed. The study was scheduled for 16 weeks with 12 months of follow-up on a monthly basis. Treatment was well tolerated by all the patients, with no adverse drug-related symptoms and no drop-outs. By the end of the study, 25/30 patients (83.3%) using the aloe vera extract cream had been cured compared with the placebo cure rate of only 2/30 (6.6%), resulting in significant clearing of the psoriatic plaques (328/396 (82.8%) vs. placebo 28/366 (7.7%), and a decreased PASI score to a mean of 2.2.

Gastric ulcers

The internal use of aloe vera gel to treat peptic ulcers was studied in 1963. Twelve patients with X-ray-confirmed duodenal ulcers were given 1 tablespoon of an emulsion of aloe vera gel in mineral oil once daily. At the end of 1 year, all patients demonstrated complete recovery and no recurrence. Based on experimental evidence, the following factors were thought to be responsible:

Aloe vera gel was shown to inactivate pepsin when no food is present in the stomach; however, when food is present, pepsin is released and allowed to digest the food.

Aloe vera gel was shown to inhibit the release of hydrochloric acid via interference with histamine binding to the parietal cells.

Aloe vera gel is an excellent demulcent, which promotes healing by preventing aggravating irritants from reaching the sensitive ulcer.

AIDS

Acemannan has demonstrated some direct antiviral activity against HIV-1 via inhibiting glycosylation of viral glycoproteins, but its main potential in the treatment of AIDS and HIV may be its enhancement of the action of a primary antiviral drug used in AIDS, azidothymidine (AZT). In vitro studies have shown that acemannan combined with suboptimal non-cytotoxic concentrations of AZT or acyclovir acts synergistically to inhibit the replication of HIV and herpes simplex type 1 (HSV-1). Based on these studies, as well as preliminary human studies, researchers believe that the use of acemannan may reduce the amount of AZT required by as much as 90%. Since AZT is not only very costly, but is also associated with severe side-effects, including anemia and granulocytopenia due to bone marrow suppression, the use of aloe vera should be considered.

Preliminary clinical studies suggest that acemannan and aloe vera may be beneficial when administered orally in HIV-positive individuals. In one study, 14 HIV patients prescribed oral acemannan (800mg/day) demonstrated significant increases in circulating monocytes/macrophages. Specifically, significant increases were seen in the number of large circulating monocytes, indicating improvement in phagocytizing, processing, and presenting cells in the blood. In another study of 15 AIDS patients receiving an oral dose of acemannan (800 mg/day), the average scores of Modified Walter Reed Clinical (MWR) scoring, absolute T-4, absolute T-8, and p24 core antigen levels all improved in those surviving at the end of 900 days. Two patients died of AIDS, and another committed suicide. From this study, as well as others, it has been suggested that prognostic criteria to determine the most responsive patients are those with an absolute T-4 count greater than 150/mm3 and p24 levels less than 300.

In another study of 30 patients, aloe vera juice (0.6L/day) was used in conjunction with essential fatty acids and a multiple vitamin, mineral and amino acid supplement. The 15 AIDS, 12 ARC and two HIV-seropositive patients continued with regular medication, including AZT. After 180 days, all patients showed clinical improvement according to modified Karnofsky Quality Of Life Assessment scores and the Modified Walter Reed Clinical Evaluation; 25% of those positive for the p24 core antigen converted to non-reactive; anemia induced by AZT showed improvement in all patients; and the patients gained an average of 7%.

Unfortunately, a more recent study did not reproduce these results. A comprehensive study assessed the safety and efficacy of acemannan as an adjunctive to antiretroviral therapy among 63 male patients (mean age, 39 years) with advanced HIV disease receiving zidovudine (ZDV) or didanosine (ddI). The randomized, double-blind, placebo-controlled trial provided a large dose of acemannan (400mg orally four times daily). Eligible patients had CD4 counts of 50-300 twice within 1 month of study entry and had received 26 months of antiretroviral treatment (ZDV or ddI) at a stable dose for the month before entry. CD4 counts were made every 4 weeks for 48 weeks. p24 antigen was measured at entry and every 12 weeks thereafter. Sequential quantitative lymphocyte cultures for HIV and ZDV pharmacokinetics were performed in a subset of patients.

The mean baseline CD4 counts were 165 and 147 in the placebo and acemannan groups, respectively; 90% of the patients were receiving ZDV at entry. Six patients in the acemannan group and five in the placebo group developed AIDS-defining illnesses. No statistically significant difference was seen between the groups at 48 weeks with regard to the absolute change or rate of decline at CD4 count. Among ZDV-treated patients, the median rates of CD4 change (ACD4) in the initial 16 weeks were -121 and -120 cells/year in the placebo and acemannan groups, respectively; ACD4 decline from week 16 to 48 was 0 and -61 cells/year in the acemannan and placebo groups (P=0.11), respectively. No statistical difference was seen between groups with regard to adverse events, p24 antigen, quantitative virology, or pharmacokinetics. Twenty-four patients, 11 receiving placebo and 13 receiving acemannan, discontinued study therapy prematurely, none due to serious adverse reactions. The decreased, but not statistically significant, rate of loss of CD4 cells in the acemannan group from weeks 16 to 48, provides a possible ray of hope that long-term use, such as reported above, may be of value and should be investigated.

Asthma

Oral administration of an extract of aloe vera for 6 months was shown to produce good results in the treatment of asthma in some individuals of various ages. However, aloe vera extract was not effective at all in patients dependent upon corticosteroids. The mechanism of action is thought to be via restoration of protective mechanisms followed by augmentation of the immune system.

The extract used in the study was produced from the supernatant of fresh leaves stored in the dark for 7 days at 4C. The dosage was 5ml of a 20% solution of the aloe extract in saline twice daily for 24 weeks. Eleven of 27 patients (40%) without corticosteroid dependence reported significant improvement at the study's conclusion.

Studies indicate that subjecting the leaves to dark and cold results in an increase in the polysaccharide fraction. One gram of the crude extract obtained from leaves stored in the cold and dark produced 400 mg of neutral polysaccharide, compared to only 30 mg produced from leaves not subjected to cold or dark.

Diabetes

Aloe vera also exhibits a hypoglycemic effect in both normal and alloxan-induced diabetic mice. A small human study of five patients with non-insulin dependent diabetes also showed benefit. When patients ingested half a teaspoonful of aloe 4 times daily for 14 weeks, fasting blood sugar in every patient fell from a mean of 273 to 151mg/dl with no change in body weight. The authors concluded that aloe lowers blood glucose levels by an unknown mechanism. A more recent and larger study (49 men and 23 women) now provides more support for the efficacy of aloe in combination with glibenclamide in diabetes. While no response occured to glibenclamide given alone, the combination was very effective. Patients were provided with 1 tablespoon of aloe gel and 5mg of glibenclamide twice a day, with 5 mg twice a day of glibenclamide serving as the control. After 2 weeks, fasting blood sugar had decreased significantly in the group using the aloe-gibenclamide combination, and by day 42 had dropped from an average of 289 mg% to a remarkable 148 mg%. The decrease in serum cholesterol was not significant, but serum triglycerides were cut almost in half, from 223mg% to 128 mg% by day 42. No adverse effects were noted using standard blood chemistries.

Contraception

Studies suggest aloe may be an effective spermicide. Twenty samples of fresh ejaculate from healthy human volunteers between 20 and 30 years of age were treated in vitro with a 1% concentration of zinc acetate combined with lyophilized Aloe barbadensis (at concentrations of 7.5-10%). The combination was shown to possess powerful spermicidal and antiviral effects that researchers theorized were due to their concentration of minerals (boron, barium, calcium, chromium, copper, iron, potassium, magnesium, manganese, phosphorus, and zinc), that were toxic to the sperm tail, causing instant immobilization. Studies using this combination with rabbit vaginal epithelium showed no irritation---in contrast to noxoygnol-9, the active spermicidal ingredient used in vaginal contraception for over 30 years, which appears to cause cell membrane damage in vaginal and cervical epithelium and may possibly have teratogenic effects.

Cancer prevention

The antigenotoxic and chemopreventive effect of Aloe barbadensis on benzo[a]pyrene (B[a]P)-DNA adducts was investigated in vitro and in vivo in an animal model. Aloe showed a time-course and dose-dependent inhibition of [3H]B[a]P-DNA adduct formation in primary rat hepatocytes, inhibited cellular uptake of [3H]B[a]P in a dose-dependent manner, and significantly inhibited adduct formation in various organs (liver, kidney, forestomach and lung). When mice were pretreated with aloe for 16 days before B[a]P treatment, inhibition of BPDE-I-DNA adduct formation and persistence was enhanced. Phase II glutathione-S-transferase activity was slightly increased in the liver, but phase I cytochrome P450 activity was not affected.

In animal cancer studies, these effects translate to protection from Norman murine sarcoma in mice and efficacy in treatment of spontaneous neoplasms in dogs and cats.

Herbs that may promote potassium loss: Theoretically, concomitant use of aloe with either horsetail plant, due to its diuretic action, or licorice rhizome, due to its potential for aldosterone-like side effects at high doses, may increase the risk of potassium depletion.

Toxicology

Drug preparations, i.e., herbal stimulant laxative drugs, have a higher general toxicity than the pure glycosides, presumably due to their aglycone content.

An aloe extract containing 23% aloin and less than 0.07% aloe-emodin, as well as aloin, produced no mutagenic effects in bacterial and mamammalian test systems.

Long-term use/abuse may result in disturbances of electrolyte balance, especially potassium deficiency, albuminuria and hematuria. Pseudomelanosis coli (pigment implantation into the intestinal mucosa) is harmless and usually reverses upon discontinuation of the drug.

The potassium deficiency can lead to disorders of heart function and muscular weakness, especially with concurrent use of cardiac glycosides, diuretics and/or corticosteriods.

Contraindications

Although rare, hypersensitivity reactions manifesting as generalized nummular eczematous and papular dermatitis as a result of topically applied aloe vera preparations have been reported.

Topical aloe preparations are not recommended for treating deep vertical wounds: Aloe vera gel has been shown to delay wound healing in cases of surgical wounds such as those produced during laparotomy or cesarean delivery.

Due to the irritating effect of its anthranoid aloins, aloe dried juice/latex should not be used by individuals with intestinal obstruction, Crohn's disease, ulcerative colitis, appendicitis, peptic ulcers, abdominal pain of unknown origin, nausea, vomiting, hermorrhoids or kidney disease. Additionally, aloe gel could be contaminated with aloe latex and should therefore be used with caution by individuals with any of these conditions.

Theoretically, overuse of aloe dried juice/latex might lead to potassium depletion, so individuals with heart conditions should use aloe dried juice/latex--or any purgative agent--with caution.

Aloe dried juice/latex should not be used by persons with hemorrhoids due to the possibility of causing stenosis, thrombosis or prolapse.